EDUCATION

Collagen Triple Helix Repeat Containing-1 (CTHRC1) Functions

The focus of our laboratory is on understanding the function of the gene Collagen Triple Helix Repeat Containing-1 (Cthrc1), which was discovered in our laboratory as a gene expressed in tissues undergoing remodeling.

Figure 1. Cthrc1 is highly induced in the outer layer (adventitia) of arteries in response to injury. This layer undergoes a significant scarring process with abundant deposition of collagen, which leads to narrowing of the artery lumen.

With genetic gain-of function and loss-of-function mouse models for Cthrc1 we seek to determine the functions of this molecule. Recent discoveries by our laboratory revealed that Cthrc1 functions as a pituitary- and hypothalamus-derived hormone with substantial circulating levels detectable in some human subjects. Evidence from genetic mouse models indicates that Cthrc1 plays a role in regulating body composition and voluntary physical activity. Increased body fat observed in Cthrc1 null mice is the result of inhibition of adipocyte differentiation by Cthrc1. The effects of Cthrc1 are mediated by inhibition of PPAR signaling, a critical signaling pathway for fat cell differentiation. Based on our findings that some healthy human subjects have substantially elevated Cthrc1 blood levels, our laboratory is interested in investigating how Cthrc1 affects metabolism, physical activity, and athletic performance both in genetic mouse models as well as in human subjects.